This project will examine mechanisms which regulate water balance in a variety of physiological and pathological conditions. Most of the relevant expertise and methodology available in this Medical Center will be brought to bear on the problems. A major emphasis will be placed on mechanisms regulating vasopressin (ADH) secretion. Studies will be performed in conscious animals and will utilize a sensitive radioimmunoassay for ADH. The role of CNS neurotransmitters and prostaglandins in regulating ADH secretion will be examined and, based on the results, pharmacological inhibitors of potential ADH-releasing substances will be examined for their ability to inhibit ADH release following both osmolar and non-osmolar stimuli. Studies will also be performed on ADH secretion in experimentally-induced circulatory disorders, electrolyte and acid-base disturbances and disorders of thyroid and adrenocortical function. The renal responsiveness to ADH in these disorders will also be examined. In studying the pathogenetic role of ADH in disorders of water balance a specific inhibitor of the hormone would be invaluable. Therefore, a systematic program of synthesis and testing of ADH analogs for anti-ADH activity is included in this proposal. Because of increasing evidence that immunologic mechanisms alter renal tubular function a systematic effort will be made to produce specific antibodies against collecting duct cells. This would provide an invaluable experimental model for studying collecting duct function and disorders of it caused by immuno mechanisms.